Regenerative medicine is highly expected to provide medical means for healing irreparable damage of body parts due to accidental injuries or diseases. In particular, development of a method for healing damaged tissues by transplantation of regenerated cells derived from the injured patient is expected to solve the problem of immune rejection, and thereby greatly reduce the burdens of patients and medical institutions. So far, regeneration of some body parts, such as skin or cornea, has been studied as a medical treatment based on such regenerative medicine.
However, currently, regenerative medicine can be applied only to the limited tissues. One of the hindrances to the advancement of regenerative medicine is the unavailability of cells capable of pluripotent differentiation and self-replication; such cells can be differentiated into various cells, tissues and organs. After the fetus period, humans develop cells capable of pluripotent differentiation and self-replication that can be differentiated into particular cells and tissues; however, humans do not have pluripotent stem cells capable of pluripotent differentiation and self-replication that can be differentiated into various cells. A method for establishing strains of embryonic stem cells (ES cell), which are pluripotent stem cells, has been developed for mice used as model organisms; however, production of human ES cells is greatly hindered by ethical restrictions, as it requires disruption of an undeveloped early embryo to obtain target cells. Therefore, individualized ES cell production for each patient has so far been virtually impossible.
Given this situation, production of induced pluripotent stem cells by way of reprogramming of somatic cells (iPS cells) is attracting attention as a technique that enables production of pluripotent stem cells from readily available somatic cells. This technique is characterized by introduction of nuclear reprogramming factors OCT3/4, SOX2, c-MYC, AND KLF4 into somatic cells (Patent Literature 1). In contrast to hitherto-known technologies, the use of an iPS cell production technique is expected to enable production of pluripotent stem cells for various patients, thus enabling regeneration of organs and nerves that have been considered irreparable.
However, some drawbacks have been reported regarding the induced pluripotent stem cells, including tumorigenesis of transplanted cells and inefficiency in the production. Such drawbacks are considerable issues in the application of the induced stem cells in clinical use. Assumed causes of tumorigenesis include introduction of proto-oncogene c-Myc and induction of cancer-inducing mutation due to introduction of genes into the genome. Regarding low efficiency in production of induced pluripotent stem cells, more trial and error is necessary to find effective induction other than the methods using genome insertion. To solve these problems, research has been conducted for (1) a method for attempting induction after removing cancer genes from the introducing cells, (2) a method using proteins or a method of introducing plasmid, and (3) a method using various virus vectors. However, so far, these methods are all insufficient for practical use in the medical industry due to insufficient introduction efficiency, etc.
Under such circumstances of the prior art, there has been a demand for the development of a technology for producing satisfactory induced pluripotent stem cells for practical use in the medical industry.